Dextromethorphan, the cough suppressant found in more than 120 over-the-counter cold and flu products, can cause full-blown psychosis when taken at high doses. So can diphenhydramine, the antihistamine sold as Benadryl. These are not obscure chemicals or black-market substances. They sit on open shelves in every pharmacy and grocery store in America, and at doses just five to ten times the recommended amount, they can produce hallucinations, delirium, and psychotic breaks that land thousands of people in emergency rooms each year.
For families managing dementia or monitoring cognitive health in aging loved ones, this is not an abstract concern. Older adults are more susceptible to the neurological effects of both drugs, and accidental overdoses — from doubling up on cold medications or forgetting a dose was already taken — can mimic or worsen dementia symptoms. A 2025 editorial in PMC went so far as to argue that diphenhydramine should no longer be available over the counter at all, given its toxicity profile and abuse potential. Meanwhile, the DEA classifies dextromethorphan as a “drug of concern” even though it remains federally unscheduled. This article examines how these two common OTC drugs produce psychosis, the specific dose thresholds where danger begins, who is most at risk, and what caregivers and families should watch for.
Table of Contents
- How Can a Common OTC Drug at High Doses Cause Psychosis?
- Dose Thresholds and Who Faces the Greatest Risk
- The Benadryl Challenge and Real-World Consequences
- What Caregivers Should Do to Reduce the Risk
- The Chronic Psychosis Risk That Most People Miss
- When Psychosis Mimics Dementia Progression
- Where Policy and Awareness Are Headed
- Conclusion
- Frequently Asked Questions
How Can a Common OTC Drug at High Doses Cause Psychosis?
The answer lies in how these drugs interact with the brain at doses far beyond their intended therapeutic range. Dextromethorphan, or DXM, works as a cough suppressant at 10 to 30 milligrams per dose. But at approximately 1,500 milligrams — roughly five to ten times the recommended amount — it begins acting on NMDA receptors in the brain, the same receptors targeted by PCP and ketamine. The result is not just drowsiness or nausea. Users at what recreational abusers call the “third plateau” of intoxication experience profound dissociation, confusion, and psychosis. A clinical case study published in PMC, titled “Dextromethorphan in Cough Syrup: The Poor Man’s Psychosis,” documented exactly these psychotic episodes in patients who had taken nothing more exotic than over-the-counter cough syrup. Diphenhydramine operates through a different but equally dangerous mechanism.
It causes what toxicologists call anticholinergic toxidrome — it blocks acetylcholine, a neurotransmitter critical for memory, attention, and coherent thought. At doses of 300 milligrams or more, moderate symptoms appear: agitation, confusion, hallucinations, and heart rhythm disturbances. At 1,000 milligrams or above, the picture turns severe, with full delirium, psychosis, seizures, coma, and death. For context, a standard Benadryl tablet contains 25 milligrams, so 300 milligrams is just 12 tablets — a quantity easily within reach of anyone with a bottle on the nightstand. The distinction between these two pathways matters clinically. DXM-induced psychosis tends to look dissociative, with the person appearing detached from reality, unresponsive, or in a trance-like state. Diphenhydramine-induced psychosis tends to look more like classic delirium — the person may be agitated, combative, talking to people who are not there, and unable to recognize familiar surroundings. For a caregiver already managing a loved one with cognitive decline, either presentation can be terrifying and easily mistaken for a sudden worsening of dementia.
Dose Thresholds and Who Faces the Greatest Risk
The gap between a therapeutic dose and a dangerous one is narrower than most people realize, especially for older adults. DXM’s recommended dose is 10 to 30 milligrams every four to six hours. But DXM is present in over 120 products — Robitussin, NyQuil, Coricidin (sometimes called “Triple C”), and dozens of store-brand equivalents. A person taking two different cold products simultaneously, or an elderly patient who forgets they already took a dose, can inadvertently push into hazardous territory. Roughly 6,000 emergency room visits per year are attributed to DXM abuse alone, according to DEA data. Diphenhydramine carries similar risks with an even more troubling demographic pattern. A study reported by Healio documented 413 diphenhydramine-related adverse events among people aged 10 to 25, with 64 percent being girls. Of those events, 62.2 percent resulted in hospitalization and 51.6 percent were fatal.
Deaths jumped from 82 between 2013 and 2019 to 131 between 2020 and 2024, a spike that coincided directly with the viral “Benadryl Challenge” on TikTok. But the risk is not limited to teenagers seeking a high. Diphenhydramine ranks among the top 15 drugs most frequently found in overdose deaths in the United States, accounting for 3.2 percent of all drug overdose deaths in a 2016 CDC study. However, if the person you are caring for is elderly and has any degree of cognitive impairment, the danger threshold may be significantly lower than the numbers above suggest. Aging bodies metabolize these drugs more slowly. Kidney and liver function decline with age, meaning the drug lingers in the system longer and reaches higher effective concentrations. An older adult who takes a standard dose of Benadryl for allergies and then another dose at bedtime for sleep — a common pattern — may experience confusion, agitation, or hallucinations that would not occur in a younger, healthier person taking the same amount. This is not psychosis in the clinical sense, but it is close enough to be indistinguishable at the bedside, and it can accelerate cognitive decline in someone already vulnerable.
The Benadryl Challenge and Real-World Consequences
The most visible example of OTC-drug-induced psychosis in recent years came not from a pharmacy error or an elderly patient’s confusion, but from social media. In 2020, the “Benadryl Challenge” went viral on TikTok, encouraging teenagers to take large quantities of diphenhydramine to hallucinate and film the results. The FDA issued a formal warning in September of that year after reports of serious injuries and deaths. The human cost was immediate and devastating. A 15-year-old girl in Oklahoma died from an overdose while attempting the challenge. In 2023, Jacob Stevens, a 13-year-old boy from Columbus, Ohio, died after spending six days in the ICU following ingestion of more than a dozen Benadryl tablets. These were not troubled kids abusing hard drugs.
They were children who found a dare on their phones and reached into the family medicine cabinet. There is no specific antidote for diphenhydramine toxicity. treatment is supportive — physostigmine for severe delirium, benzodiazepines for psychosis and seizures — and in many cases, it is simply not enough. For families dealing with dementia, this story carries a less obvious but equally urgent warning. Many households keep diphenhydramine readily accessible — in the bathroom, on the kitchen counter, in a purse. A person with dementia who is experiencing sundowning or nighttime agitation might take repeated doses of Benadryl without remembering previous doses. The resulting anticholinergic toxicity can produce hallucinations and psychotic behavior that gets attributed to the dementia itself, leading to escalation of other medications rather than identification of the actual cause. Medication management is not just about prescription drugs.
What Caregivers Should Do to Reduce the Risk
The most practical step is also the simplest: audit the medicine cabinet. Remove or lock up any product containing dextromethorphan or diphenhydramine, and replace them with safer alternatives where possible. For cough suppression, honey-based remedies or prescription-only options discussed with a physician are preferable for elderly patients. For sleep, which is the most common reason older adults take diphenhydramine, melatonin, sleep hygiene changes, or low-dose trazodone prescribed by a doctor are all safer choices that do not carry anticholinergic risk. The tradeoff is convenience. DXM-containing cough syrups work quickly and reliably.
Benadryl is cheap, familiar, and effective for allergies and insomnia. Replacing them means having conversations with doctors, possibly paying more for alternatives, and disrupting routines. But the comparison is straightforward: the benefit of a slightly easier bedtime routine does not outweigh the risk of drug-induced psychosis, falls, hospitalization, or accelerated cognitive decline. The 2025 PMC editorial arguing it is time to “say a final goodbye” to diphenhydramine makes this case in clinical terms, noting that the drug’s abuse potential and toxicity profile no longer justify its unrestricted OTC availability. For caregivers managing someone else’s medications, a written medication log — updated each time a dose is given — can prevent accidental double-dosing. This is especially important during cold and flu season, when a well-meaning family member might give cough medicine without knowing what was taken earlier in the day.
The Chronic Psychosis Risk That Most People Miss
Most discussions of OTC drug-induced psychosis focus on acute episodes — a single overdose event, an emergency room visit, a recovery. But DXM carries a less well-known and more insidious risk. A systematic review published in PMC found that DXM is specifically associated with a chronic tendency toward psychosis, distinguishing it from other OTC drugs that primarily cause acute, self-limiting episodes. In other words, repeated high-dose DXM use may not just cause temporary psychotic breaks. It may alter brain function in ways that make psychosis more likely to recur, even after the drug clears the system. This finding has particular relevance for dementia care.
Chronic DXM use — even at moderate doses taken consistently over months or years for persistent coughs — has not been studied extensively in elderly populations with pre-existing cognitive impairment. The NMDA receptor system that DXM disrupts is the same system involved in learning and memory, and it is already compromised in Alzheimer’s disease. The interaction between chronic DXM exposure and ongoing neurodegeneration remains poorly understood, which is itself a warning: absence of evidence is not evidence of safety. The limitation here is important to acknowledge. Most research on DXM-induced psychosis has focused on younger recreational users, not elderly patients taking therapeutic doses. Extrapolating directly from one population to the other is not scientifically rigorous. But the mechanistic overlap — NMDA receptor disruption in a brain already losing NMDA-dependent function — is enough to warrant caution and conversation with a neurologist or geriatrician.
When Psychosis Mimics Dementia Progression
One of the most dangerous aspects of OTC-drug-induced psychosis in elderly patients is that it looks almost identical to a sudden worsening of dementia. A person with moderate Alzheimer’s who develops hallucinations, paranoia, and agitation after inadvertently overdosing on a cold medication may be diagnosed with behavioral and psychological symptoms of dementia and started on antipsychotics — drugs that carry their own serious risks in elderly populations, including increased mortality. The actual cause, sitting in a bottle on the shelf, goes unexamined.
Emergency physicians and geriatricians increasingly recommend checking for anticholinergic drug exposure whenever an older adult presents with sudden-onset psychosis or delirium. But this only works if the treating clinician knows what medications the patient has access to, including OTC products. Caregivers can help by bringing every bottle and box from the medicine cabinet to medical appointments, not just the prescription medications. What seems like a harmless allergy pill or cough syrup may be the missing piece of a clinical puzzle.
Where Policy and Awareness Are Headed
The regulatory landscape around these drugs is slowly shifting. Many states have already enacted laws prohibiting the sale of DXM-containing products to minors under 18, a measure supported by the Consumer Healthcare Products Association. The FDA’s 2020 warning about diphenhydramine, while reactive rather than proactive, signaled a growing institutional awareness that OTC availability does not mean OTC safety. The 2025 PMC editorial calling for the end of over-the-counter diphenhydramine may represent the beginning of a more serious policy conversation about reclassifying the drug.
For families and caregivers, waiting for policy changes is not a strategy. The information already exists to make informed decisions now. Both dextromethorphan and diphenhydramine are effective drugs at appropriate doses for appropriate patients. But in the context of brain health — whether you are caring for someone with dementia, monitoring your own cognitive aging, or simply managing a household where these drugs are accessible — understanding their psychosis risk at high doses is not optional knowledge. It is essential.
Conclusion
Two of the most widely available over-the-counter drugs in America — dextromethorphan and diphenhydramine — can cause psychosis at high doses through distinct but equally dangerous mechanisms. DXM disrupts NMDA receptors, producing dissociative psychosis similar to PCP. Diphenhydramine blocks acetylcholine, causing anticholinergic delirium with hallucinations, agitation, and confusion.
Both drugs have documented fatalities, and both are particularly dangerous for older adults with cognitive impairment, where their effects can be mistaken for dementia progression. The steps to reduce risk are clear: audit medications, remove or secure OTC products containing these ingredients, use written dose logs to prevent accidental overdosing, and discuss safer alternatives with a physician. Bring all medications — including OTC products — to every medical appointment. And if an elderly loved one suddenly develops hallucinations, paranoia, or psychotic behavior, ask the simplest question first: what did they take today?.
Frequently Asked Questions
Can normal, recommended doses of Benadryl or cough medicine cause psychosis?
At standard recommended doses, psychosis is extremely unlikely in healthy adults. However, older adults with reduced kidney or liver function may experience confusion or delirium even at standard doses, particularly with diphenhydramine. The risk escalates significantly at doses of 300 milligrams or more for diphenhydramine and roughly 1,500 milligrams for DXM.
Is dextromethorphan a controlled substance?
No. The DEA classifies DXM as a “drug of concern,” but it remains unscheduled at the federal level. Many states have passed laws restricting sales to minors under 18, but adults can purchase it without a prescription anywhere in the country.
What should I do if I suspect someone has overdosed on Benadryl or a DXM-containing product?
Call 911 or Poison Control (1-800-222-1222) immediately. There is no specific antidote for diphenhydramine toxicity. Hospital treatment may include physostigmine for severe delirium and benzodiazepines for psychosis or seizures. Do not attempt to induce vomiting unless directed by a medical professional.
Can these drugs permanently worsen dementia?
The anticholinergic effects of diphenhydramine are a known risk factor for cognitive decline, and long-term use has been associated with increased dementia risk in epidemiological studies. DXM has been linked to a chronic tendency toward psychosis in a systematic review. While single acute episodes may resolve, repeated exposure in a person with existing cognitive impairment is not considered safe.
What are safer alternatives to Benadryl for sleep in elderly patients?
Non-anticholinergic options include melatonin, improved sleep hygiene practices, and prescription medications like low-dose trazodone. Second-generation antihistamines like cetirizine or loratadine are preferred for allergy relief because they have significantly less anticholinergic activity and do not cross the blood-brain barrier as readily.
Are there safer cough suppressants than DXM for someone with cognitive concerns?
Honey-based remedies have some clinical evidence supporting their effectiveness for cough suppression. Benzonatate is a prescription cough suppressant that works through a different mechanism and does not affect NMDA receptors. Always consult a physician before switching medications, particularly for someone with dementia or other neurological conditions.
